Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate in biomedical research. Rhesus are critically important in efforts to understand the pathogenesis of HIV-AIDS, to develop novel treatments and new vaccines against HIV infection. In addition, rhesus macaques are commonly used in studies of basic neurobiology, metabolic diseases such as diabetes and osteoporosis, and reproductive biology. Rhesus monkeys are important in analyses of stem cell biology. This species is also frequently used as an animal model in studies related to alcoholism, drug addiction, anxiety disorders and depression. This proposed project will dramatically increase the value and significance of this primate species for all types of biomedical research by generating a substantial amount of new information about functional genetic variation among rhesus macaques. It is now well established that genetic differences among people influence their risk of developing common diseases such as those listed above, including infectious diseases. Genetic variation can also influence the progression of disease and the responses of different people to a specific treatment. We will facilitate research on the genetic basis of disease susceptibility and response to treatment by identifying large numbers of new DNA sequence variants in functional genes within the rhesus genome. To accomplish this, we will sequence the exome (all functional gene exons) from 96 unrelated rhesus macaques, both Indian-origin and Chinese-origin animals. We will also produce whole genome sequences for 8 of those 96 animals. The exome and whole genome data will be used to identify new DNA sequence variation present in this species. We will also sequence RNA from the lymphocytes of all 96 animals to begin assessment of individual variation in gene expression within that tissue, and to correlate differential RNA expression with DNA sequence variation in the relevant genes. All the data generated will be made publically available through appropriate NCBl databases (e.g. Short Read Archive, dbVAR and dbSNP) and by creating our own public searchable on-line database of rhesus genetic variation. PUBLIC HEALTH RELEVANCE (provided by applicant): This project will advance and facilitate research in various fields by generating a large amount of novel and valuable information about genetic variation within rhesus macaques. This species is important for research related to many different human health problems. Increased knowledge of genetic variation in this primate species will allow researchers to conduct innovative studies of genetic effects on health and disease.